Targeting refractory/recurrent neuroblastoma and osteosarcoma with anti-CD3×anti-GD2 bispecific antibody armed T cells
In: Journal for ImmunoTherapy of Cancer, Jg. 12 (2024-03-01), Heft 3
Online
academicJournal
Zugriff:
Background The survival benefit observed in children with neuroblastoma (NB) and minimal residual disease who received treatment with anti-GD2 monoclonal antibodies prompted our investigation into the safety and potential clinical benefits of anti-CD3×anti-GD2 bispecific antibody (GD2Bi) armed T cells (GD2BATs). Preclinical studies demonstrated the high cytotoxicity of GD2BATs against GD2+cell lines, leading to the initiation of a phase I/II study in recurrent/refractory patients.Methods The 3+3 dose escalation phase I study (NCT02173093) encompassed nine evaluable patients with NB (n=5), osteosarcoma (n=3), and desmoplastic small round cell tumors (n=1). Patients received twice-weekly infusions of GD2BATs at 40, 80, or 160×106 GD2BATs/kg/infusion complemented by daily interleukin-2 (300,000 IU/m2) and twice-weekly granulocyte macrophage colony-stimulating factor (250 µg/m2). The phase II segment focused on patients with NB at the dose 3 level of 160×106 GD2BATs/kg/infusion.Results Of the 12 patients enrolled, 9 completed therapy in phase I with no dose-limiting toxicities. Mild and manageable cytokine release syndrome occurred in all patients, presenting as grade 2–3 fevers/chills, headaches, and occasional hypotension up to 72 hours after GD2BAT infusions. GD2-antibody-associated pain was minimal. Median overall survival (OS) for phase I and the limited phase II was 18.0 and 31.2 months, respectively, with a combined OS of 21.1 months. A phase I NB patient had a complete bone marrow response with overall stable disease. In phase II, 10 of 12 patients were evaluable: 1 achieved partial response, and 3 showed clinical benefit with prolonged stable disease. Over 50% of evaluable patients exhibited augmented immune responses to GD2+targets post-GD2BATs, as indicated by interferon-gamma (IFN-γ) EliSpots, Th1 cytokines, and/or chemokines.Conclusions This study demonstrated the safety of GD2BATs up to 160×106 cells/kg/infusion. Coupled with evidence of post-treatment endogenous immune responses, our findings support further investigation of GD2BATs in larger phase II clinical trials.
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Targeting refractory/recurrent neuroblastoma and osteosarcoma with anti-CD3×anti-GD2 bispecific antibody armed T cells
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Autor/in / Beteiligte Person: | Liu, Qin ; Thakur, Archana ; Lawrence G Lum ; Schalk, Dana ; Anthony F Shields ; Daniel W Lee ; Nai-Kong V Cheung ; Yankelevich, Maxim ; Modak, Shakeel ; Chu, Roland ; Taub, Jeffrey ; Martin, Alissa ; Schienshang, Amy ; Whitaker, Sarah ; Rea, Katie |
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Zeitschrift: | Journal for ImmunoTherapy of Cancer, Jg. 12 (2024-03-01), Heft 3 |
Veröffentlichung: | BMJ Publishing Group, 2024 |
Medientyp: | academicJournal |
ISSN: | 2023-0087 (print) ; 2051-1426 (print) |
DOI: | 10.1136/jitc-2023-008744 |
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